PAR2 absence completely rescues inflammation and ichthyosis caused by altered CAP1/Prss8 expression in mouse skin.

Détails

Ressource 1Télécharger: BIB_46D0BE62F6C8.P001.pdf (2389.19 [Ko])
Etat: Serval
Version: Final published version
ID Serval
serval:BIB_46D0BE62F6C8
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
PAR2 absence completely rescues inflammation and ichthyosis caused by altered CAP1/Prss8 expression in mouse skin.
Périodique
Nature Communications
Auteur(s)
Frateschi S., Camerer E., Crisante G., Rieser S., Membrez M., Charles R.P., Beermann F., Stehle J.C., Breiden B., Sandhoff K., Rotman S., Haftek M., Wilson A., Ryser S., Steinhoff M., Coughlin S.R., Hummler E.
ISSN
2041-1723 (Electronic)
ISSN-L
2041-1723
Statut éditorial
Publié
Date de publication
2011
Volume
2
Pages
161
Langue
anglais
Résumé
Altered serine protease activity is associated with skin disorders in humans and in mice. The serine protease channel-activating protease-1 (CAP1; also termed protease serine S1 family member 8 (Prss8)) is important for epidermal homeostasis and is thus indispensable for postnatal survival in mice, but its roles and effectors in skin pathology are poorly defined. In this paper, we report that transgenic expression in mouse skin of either CAP1/Prss8 (K14-CAP1/Prss8) or protease-activated receptor-2 (PAR2; Grhl3(PAR2/+)), one candidate downstream target, causes epidermal hyperplasia, ichthyosis and itching. K14-CAP1/Prss8 ectopic expression impairs epidermal barrier function and causes skin inflammation characterized by an increase in thymic stromal lymphopoietin levels and immune cell infiltrations. Strikingly, both gross and functional K14-CAP1/Prss8-induced phenotypes are completely negated when superimposed on a PAR2-null background, establishing PAR2 as a pivotal mediator of pathogenesis. Our data provide genetic evidence for PAR2 as a downstream effector of CAP1/Prss8 in a signalling cascade that may provide novel therapeutic targets for ichthyoses, pruritus and inflammatory skin diseases.
Mots-clé
proteinase-activated receptor-2, epidermal barrier function, epithelial sodium-channel, netherton-syndrome, serine proteases, transgenic mice, tissue distribution, cell-line, in-vivo, kappa-b
Pubmed
Web of science
Open Access
Oui
Création de la notice
31/03/2011 14:06
Dernière modification de la notice
08/05/2019 17:58
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